An atypical occurrence of Aspergillosis in leukemic patient: Brief description of a clinical case.

Herein we describe a 43 year-old Caucasian female patient with acute myeloid leukemia that developed an unconventional form of invasive Aspergillosis. For therapeutic reasons, a Groshong-type central venous catheter was positioned. Monitoring the patient's clinical conditions, positive values for C-reactive protein and galactomannan were correlated with a probably Aspergillosis. Surprisingly no pulmonary evidences were observed. Due to worsening conditions, she was re-hospitalized and a blood culture was performed, whom positivity resulted as the first clinical evidence of Aspergillus fumigatus. Further evidence about species identification was obtained by sequencing the fungal ITS region. We support the clinical value of blood culture as a decisive factor to improve the diagnosis of catheter-related Aspergillosis.

Environmental pleural plaques in residents of a Quebec chrysotile mining town.

We report four cases of pleural plaques found at autopsy in individuals who resided in or near the chrysotile mining town of Thetford Mines, Quebec, and who had never been employed in the chrysotile mining and milling industry. Three of these patients were farmers, and one was a road construction worker. Lung asbestos content of these cases was compared with that of a group of nine persons living in the same vicinity who did not have pleural plaques. The plaque group was found to have an equal chrysotile content but about a fourfold elevation in median tremolite content, a statistically significant increase. Fiber sizes were the same in both groups. Also, one plaque case had an elevated level of relatively long titanium oxide fibers. These observations suggest that environmental pleural plaques in this region of Quebec are probably caused by exposure to tremolite derived from local soil and rock and that other types of mineral fibers such as titanium oxide may occasionally also be the cause of such lesions.

Clearance of chrysotile asbestos from human lung.

In contrast to amphibole asbestos, chrysotile asbestos fails to accumulate in human lungs. The reason for this phenomenon is not known. To examine this problem, we extracted chrysotile and tremolite fibers from the lungs of 11 chrysotile miners and millers whose last exposure was within 2 years of death and 12 chrysotile miners and millers whose last exposure was greater than 12 years (7 with last exposure 12-15 years and 5 with last exposure 22-25 years) before death. Fibers were extracted by bleach digestion, and concentrations, compositions, and sizes were determined by analytical electron microscopy. Native UICC Canadian chrysotile was used as a composition standard. Compared to the standard, there was minor loss of magnesium at 2 years and additional very slight loss after 12 years. The ratio of chrysotile to tremolite concentration did not change with time. There was also no evidence of increasing fiber length with time from last exposure. These data indicate that accumulation of amphibole compared to chrysotile in human lungs does not reflect either long-term dissolution of chrysotile or long-term preferential clearance of chrysotile compared to amphibole. Contrary to results of animal studies, fiber length in humans does not increase with time since last exposure. These findings imply that the failure of chrysotile to accumulate in human lungs reflects events that occur early after exposure rather than long-term clearance mechanisms.

Mineralogic parameters related to amosite asbestos-induced fibrosis in humans.

We have previously shown that in the lungs of a group of chrysotile miners and millers, grade of interstitial fibrosis (asbestosis) is directly proportional to tremolite fiber or chrysotile fiber concentration but is inversely proportional to mean fiber length and length-related parameters. To compare the effects of the commercial amphibole asbestos amosite on parenchymal fibrosis, we histologically graded fibrosis in four different sites in the lungs of 20 shipyard and insulation workers with heavy amosite exposure and measured by analytic electron microscopy fiber concentration and size in corresponding portions of lung tissue. Fibrosis grade was found to be strongly positively correlated with amosite concentration and negatively correlated with mean fiber size parameters, including fiber length, width, surface area, and mass. A comparison of our present results with our data on the chrysotile miners and millers showed that the regression lines of fibrosis grade versus concentration for amosite, chrysotile, and tremolite were statistically different. These findings indicate that amosite concentration, like chrysotile and tremolite concentration, is closely and directly related to fibrosis at the local lung level. Furthermore, these observations again raise the possibility that short fibers may be more important than is commonly believed in the genesis of fibrosis in man. Last, the concentration comparison data indicate that, fiber for fiber, amosite is more fibrogenic than is chrysotile or tremolite, and indirectly suggest that tremolite is more fibrogenic than is chrysotile.

Rapid short-term clearance of chrysotile compared with amosite asbestos in the guinea pig.

Compared with amphibole forms of asbestos, chrysotile asbestos fails to accumulate in lung tissue; the mechanism of this effect is disputed. To investigate this problem, we administered a mixture of the amphibole, amosite, and chrysotile to guinea pigs by intratracheal instillation. At 1 day, 1 week, and 1 month after instillation, animals were killed, and the numbers, types, sizes, and compositions of fibers in the lungs were determined by analytical electron microscopy. Both chrysotile and amosite fiber concentrations decreased with time, but relative chrysotile clearance was significantly greater than amosite clearance. There was no evidence of magnesium leaching from chrysotile fibers of any size at any time. Analysis of fiber lengths and widths showed a time trend toward shorter and narrower fibers (particularly toward fibers of less than 2 microns long and less than 0.025 microns wide) for chrysotile. This effect was not seen for amosite. We conclude that (1) failure of chrysotile accumulation in lung results from preferential chrysotile clearance during the first few days to weeks after exposure; (2) there is no evidence that fiber dissolution plays a role in chrysotile clearance; (3) preferential clearance may be a result of fragmentation and rapid removal of chrysotile fibers.

Mineralogic correlates of fibrosis in chrysotile miners and millers.

To determine which mineral parameters relate to the degree of interstitial fibrosis (asbestosis) in the lungs of chrysotile miners and millers, we graded fibrosis histologically and correlated fibrosis grades with fiber concentration and mean size, surface area, and mass, and with total sample fiber length, surface area, and mass in 21 cases. A positive correlation of fibrosis grade with tremolite concentration and a lesser correlation with chrysotile concentration was found for whole lungs, specific sites within lungs, and, for tremolite, single microscopic fields. No correlations were found for measures of chrysotile fiber size, surface area, or mass, but tremolite mean fiber length, aspect ratio, and surface area were, surprisingly, negatively correlated with fibrosis grade. Measures based on total rather than on mean case or site parameters failed to show correlations with fibrosis. We conclude that: (1) degree of pulmonary fibrosis reflects fiber concentration at both a bulk and a microscopic level; (2) mean fiber length and parameters related to mean fiber length also correlate with fibrosis grade, but, contrary to predictions from animal studies, this correlation is negative, suggesting that short fibers may be more important in the genesis of pulmonary fibrosis than is commonly believed; (3) there is no evidence that parameters such as total fiber length, surface area, or mass provide predictors of degree of fibrosis.

Lung asbestos content in chrysotile workers with mesothelioma.

The role of chrysotile asbestos in the genesis of mesotheliomas in humans is disputed. We analyzed the asbestos content of the lung in 6 long-term chrysotile miners and millers who had pleural mesotheliomas. In five patients, only chrysotile ore components (chrysotile and tremolite/actinolite/anthophyllite types of amphibole asbestos) were found, while the sixth patient presented both chrysotile ore components and amosite, a type of asbestos that is not derived from the mining process. The mean number of fibers/g dry lung for the 5 patients with mesothelioma containing only chrysotile ore components was higher (chrysotile 64 X 10(6) and tremolite group 540 X 10(6] than in a group of long-term chrysotile miner control subjects who had no asbestos-related disease (chrysotile 23 X 10(6), tremolite group 58 X 10(6], but some patients with mesothelioma had fiber burdens near the mean of the control range. Fiber sizes and aspect ratios in the mesothelioma group were approximately the same as those in the control subjects, and analysis of fiber distribution failed to show any preferential localization in the periphery of the lung. However, the concentration ratio of tremolite in the lungs of the mesothelioma cases compared to the control cases was 9.3, while the ratio of chrysotile was only 2.8. Our findings provide strong evidence that chrysotile mine dust (chrysotile and amphibole components) can produce mesotheliomas in humans; the greater relative amounts of tremolite group amphiboles present in the patients with mesothelioma raise the possibility that these fibers may be important in the pathogenesis of the tumors.

Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome.

Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow and it is quite effective in revealing marrow involvement in hematological malignancies. MRI has been compared with needle marrow biopsy in 22 patients with myelodysplastic disorders. A fairly good concordance has been demonstrated in 79% of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was not generalized. Therefore in elderly patients with MDS, MRI of the spine allows the quantification of bone marrow hyperplasia with a greater accuracy than bone marrow biopsy and this may be useful for monitoring the effect of cytostatic treatment.

Trisomy 11 in myelodysplastic syndrome-derived acute myeloblastic leukaemias.

Here we report 3 cases of trisomy 11 observed in 1 patient with secondary acute myeloblastic leukaemia and in 2 patients with spontaneous acute myeloblastic leukaemia. In all 3 patients, the picture of overt acute leukaemia arose following a clinically established myelodysplastic syndrome. These findings, together with the previously reported occurrence of trisomy 11 in myelodysplastic syndrome and in acute myeloblastic leukaemia, suggest that this abnormality can be considered specifically associated with myelodysplastic syndrome and with the subsequent and related acute myeloblastic leukaemia.

Serum erythropoietin level and marrow erythroid infiltration predict response to recombinant human erythropoietin in myelodysplastic syndromes.

BACKGROUND AND METHODS: In 38 patients with myelodysplastic syndromes (MDS) the values of serum erythropoietin were measured at diagnosis and compared with the haemoglobin level. A highly significant inverse relationship was found between these two parameters, suggesting that the physiologic mechanism of erythroid progenitor cell recruitment is preserved in MDS. Fourteen transfusion-dependent patients were treated with recombinant human erythropoietin at the dose of 150 U/Kg three times weekly for at least 2 months. RESULTS AND CONCLUSIONS: Under recombinant human erythropoietin, three patients became transfusion-independent and 5 had a transient decrease of their transfusion requirement. Two patients under prolonged treatment at the same dose of erythropoietin remain in complete remission after 12 and 15 months respectively. A direct relationship between response to erythropoietin treatment and degree of bone marrow erythroid hyperplasia, coupled to an inverse correlation between response to erythropoietin and baseline serum erythropoietin levels were noted. Based on these findings, recombinant human erythropoietin may represent an effective treatment modality for selected patients with MDS.

Role of thoracic computed tomography in the treatment plan of Hodgkin's disease.

Conventional chest X-rays and CT scans, performed at the time of the initial staging in 67 patients affected by Hodgkin's disease, were reviewed and compared. CT scans provided evidence of disease not shown by concomitant conventional chest X-rays in 10 patients (15%). The impact on patient management of the additional CT data was evident in 8 cases (11.9%), either changing the whole treatment plan (4 patients) or enlarging radiation ports (4 patients). Traditional prognostic features did not influence the outcome, and only hilar adenopathy adversely affected event-free survival, without however reaching statistical relevance (p greater than 0.05). Our data suggest that thoracic CT scan is helpful in drawing up the treatment plan, while its role in identifying new prognostic factors is still uncertain.

[Magnetic resonance in the study of residual mediastinal masses after therapy of lymphoma]. / La risonanza magnetica nello studio delle masse mediastiniche residue dopo terapia nei linfomi.

Forty-five patients with mediastinal spread of malignant, Hodgkin's and non-Hodgkin's lymphomas were examined with MR Imaging at 0.5 T. Ninety-two examinations were performed at diagnosis and/or during and after treatment to investigate MR capabilities in distinguishing fibrous tissue from active disease in the masses residuing after therapy--which cannot be done by means of CT. MR results indicated T2-weighted sequences to be the most useful. MR results were compared with the data collected from follow-up, clinics, and biology. MR Imaging had high accuracy (92.1%). The number of false negatives was very low, thanks to the low intensity of fibrous tissue, while a relatively high number of false positives was observed, probably due to the difficulties in discriminating inflammatory from neoplastic tissue.

Results of a low aggressivity chemotherapy regimen (CVP/CEB) in elderly Hodgkin's disease patients.

BACKGROUND: Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy regimens devised for elderly HD patients. PATIENTS AND METHODS: From 1990 to 1993, 25 elderly HD patients were treated with the CVP/CEB regimen: chlorambucil 6 mg/sqm p.o. days 1 through 7, vinblastine 6 mg/sqm i.v. on day 1, procarbazine 100 mg/sqm p.o. days 1 through 7, prednisone 30 mg/sqm p.o. days 1 through 7, cyclophosphamide 500 mg./sqm i.v. day 15, etoposide 70 mg/sqm i.v. day 15, bleomycin 10 mg/sqm i.v. day 15. Each course was repeated every 4 weeks. Stage I and II patients were treated with 3 courses followed by involved field radiotherapy, while more advanced stage patients received 6 courses and radiotherapy was limited to bulky areas. The results of the CVP/CEB regimen are retrospectively compared to those of 74 elderly patients treated between 1982 and 1989 and subdivided into the following 2 groups: 32 patients treated according to the same therapy used at that time in younger patients, and 42 patients given alternative low aggressivity or palliative treatment. RESULTS: CVP/CEB is a well-tolerated regimen, with only 1 (4%) toxic death and 2 (8%) protocol violations/interruptions. The CVP/CEB complete remission rate (73%) compares favorably with our previous groups of patients, mainly because of the lower toxic death rate. However, the CVP/CEB relapse-free survival rate is lower than that of patients treated with more aggressive conventional regimens (47% vs. 77%, p < 0.02). The CVP/CEB overall survival and event-free survival rates are 55% and 32%, respectively, and they are not statistically different from those of patients treated before 1990. CONCLUSIONS: CVP/CEB is a well-tolerated low toxicity regimen with a high CR rate. The relapse rate is high and event-free survival is comparable to that of patients treated conventionally. Our results suggest the need for individualized treatment criteria for older patients with HD.

Probability of cure in elderly Hodgkin's disease patients.

BACKGROUND: Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of trials designed for them, useful information can be obtained only by retrospective analyses. METHODS: We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity. RESULTS: In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns). CONCLUSIONS: Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.